Biology and treatment of metastatic gastrointestinal neuroendocrine tumors

Abstract

Neuroendocrine malignancies of the gastroenteropancreatic axis include carcinoid and pancreatic endocrine tumors. These heterogeneous neoplasms arise from the enterochromaffin cells of the gastrointestinal tract and the islet cells of the pancreas. Histologically, most well-differentiated endocrine tumors consist of small, round, monomorphic cells, arranged in islands or trabeculae, with a distinct "salt-and-pepper" pattern of nuclear chromatin. Chromogranin and synaptophysin are useful as immunohistochemical markers of neuroendocrine differentiation. Other common features include the capacity to secrete peptide hormones and biogenic amines. A relatively indolent growth rate is characteristic of most gastrointestinal neuroendocrine tumors, with the exception of poorly differentiated tumors which are usually aggressive. Treatment strategies are designed to limit tumor progression and palliate hormonal syndromes. This article reviews the diverse biologic characteristics of gastrointestinal neuroendocrine tumors and current treatment options for metastatic disease.

Figure 1.

Distribution of gastrointestinal carcinoid tumors by primary tumor site.

Figure 2.

Relationship between tumor size and frequency of distant metastases in carcinoid tumors of the small intestine (2a), appendix (2b), and rectum (2c).

Figure 3.

Metastatic carcinoid tumor to the root of the mesentery (arrow) causing typical circumferential desmoplastic fibrosis.

Figure 4:

Examples of well differentiated (4a), poorly differentiated (4b), and moderately differentiated (4c) gastrointestinal neuroendocrine tumors. Photographs courtesy of Nasir Aejaz, MD, Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.